Abstract
The renin-angiotensin system (RAS) is a highly complex hormonal cascade that spans multiple organs and cell types to regulate solute and fluid balance along with cardiovascular function. Much of our current understanding of the functions of the RAS has emerged from a series of key studies in genetically-modified animals. Here, we review key findings from ground-breaking transgenic models, spanning decades of research into the RAS, with a focus on their use in studying blood pressure. We review the physiological importance of this regulatory system as evident through the examination of mouse models for several major RAS components: angiotensinogen, renin, ACE, ACE2, and the type 1 A angiotensin receptor. Both whole-animal and cell-specific knockout models have permitted critical RAS functions to be defined and demonstrate how redundancy and multiplicity within the RAS allow for compensatory adjustments to maintain homeostasis. Moreover, these models present exciting opportunities for continued discovery surrounding the role of the RAS in disease pathogenesis and treatment for cardiovascular disease and beyond.